Our objective is to determine the molecular and genetic basis for the differences in V[unreadable]kappa[unreadable] repertoires expressed by different inbred strains of mice and to elucidate the detailed structural organization of the mouse V[unreadable]kappa[unreadable] gene family. The studies bear upon: (1) the origin of the amino acid sequence diversity of immunoglobulin L chain V regions; (2) the role, if any, of regulatory phenomena in determining which V[unreadable]kappa[unreadable] genes will be expressed in an individual and hence, which genes will contribute to antibody responses; and (3) the possibility that the presence in or absence from the germ line of structural genes encoding V[unreadable]kappa[unreadable] regions or regulatory phenomena affecting their expression might explain immune response gene (Ir-gene) differences or differences in idiotype expression that map to immunoglobulin loci. Specific aims include: (1) DNA cloning and characterization at the DNA level of a new group of V[unreadable]kappa[unreadable] regions, called V[unreadable]kappa[unreadable]Ser, and other unique V[unreadable]kappa[unreadable] groups that are expressed only by mice bearing the Lyt-2[unreadable]a[unreadable], Lyt-3[unreadable]a[unreadable] genotype; (2) If genes for V[unreadable]kappa[unreadable] groups that show strainspecific expression are present in the genome of strains that do not express them, we will determine by nucleotide sequence analysis whether defects in associated sequences involved in V-J joining, RNA splicing, or other functions involved in gene expression may be responsible for their nonexpression; and (3) We will determine the arrangement in the germ line of the 4 to 8 V[unreadable]kappa[unreadable] genes thought to determine a single V[unreadable]kappa[unreadable] group. We will determine the long-range organization of the V[unreadable]kappa[unreadable] gene family. These studies should provide information on the evolution, stability, and possibly the function of the complex V[unreadable]kappa[unreadable] locus. (CS)